Paired Pulse Transcranial Magnetic Stimulation

The application of paired pulse transcranial magnetic stimulation (ppTMS) has become a very popular method of using TMS to probe intracortical circuits, particularly within the motor cortex . In paired-pulse paradigms, the pulse delivered first is called the conditioning pulse, while the second pulse is known as the test pulse. The outcome measure is the MEP evoked by the second test pulse, reflecting the impact of the conditioning pulse on the intracortical neural circuit.


A number of different protocols arose from the paired-pulse method of applying TMS. The principle protocols are short intracortical inhibition (SICI), intracortical facilitation (ICF), and long intracortical inhibition (LICI).

With SICI, a 1-5ms interval is required in between the conditioning pulse and the test pulse. For SICI to be present, a 1-5ms interval between pulses must be recruited along with an appropriate intensity of the conditioning and test pulses. The conditioning pulse must be subthreshold with an intensity of between 60-80% of resting motor threshold, or 70-90% of active motor threshold2. The conditioning pulse, on the other hand, needs to be suprathreshold with an MEP amplitude of ~1.5mV.

SICI is thought to rely on a conditioning pulse activating a population of inhibitory neurons within the motor cortex, which have a lower threshold than the neurons activated by the second, supra threshold test pulse. The inhibitory population is thought to involve GABAA receptors as the administration of GABAA agonists increase the magnitude of the SICI3. Kujirai et al (1993) also noted, however, that increases in MEP amplitude were observed when 10ms-15ms intervals separated the test pulse form the conditioning pulse, suggesting that paired pulse paradigms can also produce increases in MEP amplitude, depending on the interval between pulses.

The phenomena where increases in MEP amplitude take place when a subthreshold conditioning pulse is used suggests that excitatory circuits can also be probed by paired pulse TMS. The increase in MEP amplitude following presentation of a sub-threshold conditioning pulse with a 10-15ms interval between pulses produced a phenomena known as intracortical facilitation (ICF). ICF is thought to rely on an NMDA-dependent mechanism, as administration of NMDA antagonists (dextromethorphran) decreases the magnitude of ICF4.

Valls-Solé et al. (1992) varied the interval between pulses in addtion to varying the intensity of a suprathreshold conditioning pulse during voluntary contraction. When the intensity of the conditioning pulse was greater than 110% of resting motor threshold, the MEP evoked by the test pulse was suppress when the interval between these pulses ranged between 60-150ms5. Given that suppression occurs at a different timeframe to SICI, site of action is likely to differ between these two paradigms. This was conﬁrmed by an experiment that administered Baclofen, a GABAB agonist, which increased LICI 90 minutes after drug administration6.

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